Antibiotics of limited water solubility have been formulated for parenteral application either as aqueous suspensions, or by preparing water soluble derivatives (e.g., salts, esters or complexes) of the parent compound, which upon administration are either in equilibrium with the parent compound, or which are transformed back into the parent compound in the patient's system. Inherent in these practices are several problems. Use of solids in suspension severely limits the mode of parenteral administration. Furthermore, preparation of pharmaceutically acceptable solid derivatives is frequently accompanied by significant yield losses. Moreover, some otherwise desirable derivatives cannot be isolated in suitable form altogether (e.g., in pure crystalline or other stable forms).
U.S. Pat. No. 3,940,483 to Dursch discloses blending solid antibiotics of limited water solubility which are either acidic, basic, or amphoteric in nature (such as cephradine) as dry powders with suitable solid additives, such as alkali metal carbonates, for example sodium carbonate, alkali metal bicarbonates, for example sodium bicarbonate, ammonium carbamate, alkali metal or ammonium phosphates, for example sodium or potassium phosphate, organic amines like N-methylglucamine, tris(hydroxymethyl)aminomethane and the like, alkali metal hydrogen sulfates, for example sodium or potassium hydrogen sulfate, and organic acids like citric acid, tartaric acid or maleic acid. Upon addition of water to such dry mixtures, physiologically acceptable solutions of water soluble salts of the antibiotic are formed in situ and can be administered without delay. However, lactated Ringer's solution must not be used in place of water in formulating injectable cephradine blended with sodium carbonate because a precipitate of CaCO.sub.3 can form. Moreover, the sterile cephradine for injection (sodium carbonate blend) has been found to be reasonably well tolerated although there has been some evidence of discomfort on administration.